Can anxiety cause elevated D-dimer (D-dimer) levels?

Can Anxiety Cause Elevated D-dimer Levels?

Yes, anxiety can cause elevated D-dimer levels due to its effects on the coagulation and fibrinolytic systems, though the elevation is typically mild compared to levels seen in conditions like venous thromboembolism or aortic dissection. 1

Physiological Mechanism

• Anxiety triggers a stress response that affects hemostasis through multiple pathways:

  • Increases procoagulant factors (factor VIII, fibrinogen, von Willebrand factor) 1
  • Enhances platelet aggregability 1
  • Stimulates tissue plasminogen activator (tPA) release from endothelial and chromaffin cells 1
  • This tPA release leads to increased fibrinolysis, which generates D-dimer as a byproduct 1, 2

• The fight-or-flight response during anxiety creates a balance between:

  • Procoagulant changes (to reduce bleeding risk in case of injury) 1
  • Fibrinolytic activation (to prevent unwanted intravascular thrombosis) 1

Evidence from Clinical Studies

• Research has demonstrated that acute mental stress and anxiety symptoms correlate with increases in D-dimer levels 2
• In elderly subjects, Hamilton Anxiety Scale scores uniquely explained 8% of variance in resting D-dimer levels and 17% of variance in stress-induced D-dimer changes 2
• Vital exhaustion and depressive symptoms (often comorbid with anxiety) are associated with altered D-dimer responses to acute psychosocial stress 3

Clinical Significance and Interpretation

• While anxiety can elevate D-dimer, the magnitude of elevation is typically modest compared to levels seen in serious conditions 4, 5:

  • Venous thromboembolism typically shows D-dimer >0.5 μg/mL 4
  • Extremely elevated D-dimer (>5000 μg/L) is highly specific for serious illness (VTE, sepsis, cancer) 5

• When evaluating elevated D-dimer in anxious patients:

  • Consider the degree of elevation - mild elevations may be attributable to anxiety 2
  • Extremely high D-dimer levels (>10x normal) warrant thorough investigation regardless of anxiety status 5
  • Nearly half of all emergency department patients have elevated D-dimer levels, with higher levels associated with increased hospital admission and mortality 6

Diagnostic Approach

• For patients with anxiety and elevated D-dimer:

  • Assess for clinical signs and symptoms of thrombotic disorders 4
  • Consider the magnitude of D-dimer elevation - mild elevations may be anxiety-related 2
  • Use clinical decision rules (like Wells score for PE/DVT) to guide further testing 7
  • A normal D-dimer has high negative predictive value and could help exclude thrombosis 7, 4

• Important caveats:

  • D-dimer has high sensitivity but low specificity for thrombotic events 4
  • Never rely solely on D-dimer to rule out serious conditions if clinical suspicion is high 7, 4
  • A normal D-dimer according to sensitive immunoassay may help identify patients with low probability of cerebral venous thrombosis 7

Clinical Implications

• In patients with known anxiety presenting with elevated D-dimer:

  • Rule out serious conditions first (VTE, aortic dissection, etc.) 4
  • Consider repeating D-dimer measurement when the patient is less anxious 2
  • Recognize that anxiety and thrombotic conditions can coexist 1

• For patients with extremely elevated D-dimer (>5000 μg/L), maintain high clinical suspicion for serious underlying disease even if anxiety is present, as 89% of such patients have VTE, sepsis, and/or cancer 5